**3.1 Biopharmaceutical classification of oral antimicrobials**

This is a system of classifying antimicrobials based on aqueous solubility and intestinal permeability. The four major factors being considered in this classification system are dosage form, dissolution rate, solubility and permeability. Hence, antimicrobials are tested in vitro and classified into four classes:

Class 1: High solubility � high permeability

Class 2: Low solubility � high permeability

Class 3: High solubility � low permeability

Class 4: Low solubility � low permeability

All the classes of dissolution can occur in a pH range of 1–2, 4–5 and 6–8 [46]. Nevertheless, administration of highly toxic antimicrobials such as aminoglycosides (e.g. gentamicin) should be monitored since it damages the kidney.

Such drugs are said to have narrow therapeutic range NTR ð Þ

<sup>¼</sup> Minimum toxic concentration MTC ð Þ

Median effective concentration MEC ð Þ

### **3.2 Pharmacokinetic equations of antimicrobials**

Bioavailability, absorption half-life (T<sup>1</sup> /2α), mean absorption time (MAT), mean residence time (MRT), apparent volume of distribution (Vd), volume of distribution, steady state (Vdss), area under curve (AUC), area under the first moment curve (AUMC), peak time (Tmax), elimination half-life (T<sup>1</sup> /2β) and systemic clearance (Cl) are the pharmacokinetic parameters commonly determined in all species of animals and humans [7, 9, 47–49]. The most important of all these parameters are elimination half-life, volume of distribution and plasma concentration of the antimicrobials.

The pharmacokinetic process of antimicrobials in goats obeys first-order kinetic (**Figures 1** and **2**) which could be mono-exponential or bi-exponential. The exponential equation commonly used for determination of pharmacokinetic parameters is CP = Ae <sup>α</sup><sup>t</sup> + Be �βt . Other equations are:

$$\text{T1}/2\text{a} = \frac{0.693 \times \text{MAT}}{\text{ka}} \tag{1}$$

$$\mathbf{MAT} = \mathbf{1}/\mathbf{ka} \tag{2}$$

$$\text{MRT} = \frac{\text{AUMC}}{\text{AUC}} \tag{3}$$

$$\text{Vd} = \frac{\text{Clb}}{\text{ $\beta$ }} \tag{4}$$

$$\text{AUC} = \frac{\text{Dose}}{\text{Cl}} \tag{5}$$

$$\text{AUMC} = \text{MRT} \times \text{AUC} \tag{6}$$

$$\text{T1}/2\mathfrak{\beta} = \frac{\text{0.693}}{\mathfrak{\beta}}\tag{7}$$

$$\text{Clb} = \frac{\text{Dose}}{\text{AUC}} \tag{8}$$

**Figure 2.**

**143**

**Figure 1.**

*following intramuscular administration.*

*Mean plasma concentration-time curves of sulfadimidine (100 mg/kg) when co-administered with piroxicam*

*Mean plasma concentration-time curves of sulfadimidine (100 mg/kg) in male and female WAD goats*

*Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats*

*DOI: http://dx.doi.org/10.5772/intechopen.84551*

*(5 mg/kg) to male and female WAD goats following intramuscular administration.*

However, peak time (Tmax) and Cmax can be estimated from the pharmacokinetic graph [47].

*Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats DOI: http://dx.doi.org/10.5772/intechopen.84551*

**Figure 1.** *Mean plasma concentration-time curves of sulfadimidine (100 mg/kg) in male and female WAD goats following intramuscular administration.*

**Figure 2.**

*Mean plasma concentration-time curves of sulfadimidine (100 mg/kg) when co-administered with piroxicam (5 mg/kg) to male and female WAD goats following intramuscular administration.*

**3.1 Biopharmaceutical classification of oral antimicrobials**

microbials are tested in vitro and classified into four classes:

(e.g. gentamicin) should be monitored since it damages the kidney.

Class 1: High solubility � high permeability Class 2: Low solubility � high permeability Class 3: High solubility � low permeability Class 4: Low solubility � low permeability

*Goats (Capra) - From Ancient to Modern*

**3.2 Pharmacokinetic equations of antimicrobials**

curve (AUMC), peak time (Tmax), elimination half-life (T<sup>1</sup>

. Other equations are:

Bioavailability, absorption half-life (T<sup>1</sup>

tion of the antimicrobials.

<sup>α</sup><sup>t</sup> + Be �βt

is CP = Ae

netic graph [47].

**142**

This is a system of classifying antimicrobials based on aqueous solubility and intestinal permeability. The four major factors being considered in this classification system are dosage form, dissolution rate, solubility and permeability. Hence, anti-

All the classes of dissolution can occur in a pH range of 1–2, 4–5 and 6–8 [46]. Nevertheless, administration of highly toxic antimicrobials such as aminoglycosides

Such drugs are said to have narrow therapeutic range NTR ð Þ

residence time (MRT), apparent volume of distribution (Vd), volume of distribution, steady state (Vdss), area under curve (AUC), area under the first moment

clearance (Cl) are the pharmacokinetic parameters commonly determined in all species of animals and humans [7, 9, 47–49]. The most important of all these parameters are elimination half-life, volume of distribution and plasma concentra-

The pharmacokinetic process of antimicrobials in goats obeys first-order kinetic (**Figures 1** and **2**) which could be mono-exponential or bi-exponential. The exponential equation commonly used for determination of pharmacokinetic parameters

T1*=*2<sup>α</sup> <sup>¼</sup> <sup>0</sup>*:*<sup>693</sup> � MAT

MRT <sup>¼</sup> AUMC

Vd <sup>¼</sup> Clb

AUC <sup>¼</sup> Dose

T1*=*2<sup>β</sup> <sup>¼</sup> <sup>0</sup>*:*<sup>693</sup>

Clb <sup>¼</sup> Dose

However, peak time (Tmax) and Cmax can be estimated from the pharmacoki-

/2α), mean absorption time (MAT), mean

ka (1)

AUC (3)

<sup>β</sup> (4)

Cl (5)

<sup>β</sup> (7)

AUC (8)

MAT ¼ 1*=*ka (2)

AUMC ¼ MRT � AUC (6)

/2β) and systemic

<sup>¼</sup> Minimum toxic concentration MTC ð Þ Median effective concentration MEC ð Þ

$$\text{Dosage rate} \left( \text{DR} \right) = \frac{\text{bioavailability} \left( \text{F} \right) \times \text{dose} \left( \text{D} \right)}{\text{dosage interval } \left( \text{DI} \right)} \tag{9}$$

$$\text{DR} = \frac{\text{plasma concentration (CP)}}{\text{body clearance (Clb)}} \tag{10}$$

maintenance dose of 13.95 mg/kg at an 8-h interval, respectively [8]. Plasma concentration of levofloxacin is higher in healthy goats (15.51 1.41 μg/ml) than mastitis goats (12.48 1.36 kg/ml). This plasma concentration does not affect

*Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats*

enrofloxacin (2.5 mg/kg) are 5.39 0.96 h, 1.14 0.09 μg/ml and 0.83 0.13 h, respectively [51]. Gatifloxacin (5 mg/kg) provided minimum inhibitory concentration (MIC) of 0.1–2 μg/ml for susceptible microorganisms between 6 and 12 h in healthy and febrile goats, respectively [32]. Elimination half-life (3.98 0.18 h), Cmax (9.24 1.2 μg/ml), MRT (4.13 0.16 h), Vdss (1.22 0.06 L/kg) and Clb (0.24 0.01 l/h/kg) of enrofloxacin (5 mg/kg) have been reported [6]. The Vd

persistence of lincomycin in goat as it can be repeated every 24 h with MIC (0.6 μg/ml) for treatment of febrile bacterial infections in goats [33]. But intramuscular lincomycin

Vancomycin was initially active against methicillin-resistant *Staphylococcus*, but

presently vancomycin-resistant *Staphylococcus* has emerged, and vancomycinresistant *Enterococcus* has also emerged due to its usage as feed additive. Hence, prophylactic use of antibiotics should be highly reduced [52]. Concentration of pefloxacin (0.25 μg/ml) was maintained in plasma for 6–10 h after oral or intravenous administration. Therefore, intravenous pefloxacin (20 mg/kg) every 6 h or thrice orally is effective against sensitive pathogenic microbes in goats [36]. But

(3.33 1.42 h), Vdss (3.37 0.8 l/kg) and Clb (19.59 9.05 ml/min/kg), respectively, should be administered every 12 h [53]. Cefpirome (10 mg/kg) every 12 h is *useful when administered intravenously in goats. It is 19.9% plasma protein bound* [37]

sulfadimidine, warfarin, non-steroidal anti-inflammatory drugs and barbiturates. The long half-life of azithromycin after intravenous (45.2 h) and intramuscular (32.5 h) administration and MRT of 40.1 h and 60.3 h and bioavailability of 92.2% [38] show that the drug could be administered every 2 and 3 days, respectively. But half-life (67.2 h) of tulathromycin (25 mg/kg) indicates that the withdrawal period of tulathromycin may be long and there may not be a need for repeated doses of the drug. But elimination of erythromycin is higher in lactating goats (3.18 1.32 h) than non-lactating goats (1.41 1.20 h) [39] signifying that erythromycin is quickly removed from the body of non-lactating goats. MIC of erythromycin against *Staphylococcus aureus* was 0.50 and 0.75 μg/ml [54], respectively. Tylosin (10–15 mg/kg) was administered to goats both intramuscularly and intravenously. The intramuscular bioavailability was 72.6%, and serum protein binding was 37.6%, Cmax

respectively. Hence, tylosin should be injected every 14 h [43]. Gentamicin (4 mg/kg), amikacin (10 mg/kg), tobramycin (5 mg/kg), kanamycin (10 mg/kg) and apramycin (20 mg/kg) may have synergistic or additive antibacterial activity [55]. Intramuscular

and so may compete weakly with other plasma-binding drugs such as

/2β (9.99 2.83 h) suggest long

/2β (2.72 1.04 h), MRT

/2β (3.04 h), Tmax (4.19 h) and Clb (6.8 ml/kg/min),

(3.35 0.45 L/kg), Clb (0.28 0.03 l/h/kg) and T1

intravenous dose (10 mg/kg) of ciprofloxacin with T<sup>1</sup>

can be administered every 12 h [34].

(2.38 μg/ml), Vd (1.7 L/kg), T1

**145**

Since various brands of enrofloxacin have different pharmacokinetic parameters such as half-life (3.93 0.46; 4.04 0.53; 4.56 1.24 h) and plasma concentrations (15.53 1.31; 6.75 0.56; 10.40 2.65 μg/ml) [28], dosage formulations may have sufficient effects on pharmacokinetics and pharmacodynamics of aminoglycosides. Serum concentration of gentamicin (5 mg/kg) was maintained at 1.5–12 μg/ml for a period of 6 h. But gentamicin (2.5–3.0 mg/kg i.m.) every 8 h is therapeutically useful with less risk of nephrotoxicity [29], as daily intravenous administration of 4 mg/kg is effective for 36 h in the treatment of systemic and urinary tract infections caused by Gram-negative pathogens in goats [30]. Therefore, optimal dosage regimen, bioequivalence and kinetic parameters of antimicrobials are of clinical importance [31]. Elimination half-life, Cmax and Tmax of intramuscular

levofloxacin elimination [9].

*DOI: http://dx.doi.org/10.5772/intechopen.84551*

Infusion rate Ro ð Þ¼ plasma concentration*,*steady state Cpss ð Þ� Clb (11)

$$\text{Accumulation index} = \frac{1}{\text{fraction lost per doing interval}}\tag{12}$$

$$\eta = \frac{1}{1 - \text{fraction left in the body}} \tag{13}$$

$$\text{Loading dose} \left( \text{LD} \right) = \frac{\text{target Cap} \times \text{Vss}}{\text{F}} \tag{14}$$

$$\text{LD} = \text{maintenance dose (MD)} \times \text{accumulation index (Al)} \tag{15}$$

$$\text{MD} = \frac{\text{DR} \times \text{DI}}{\text{F}} \tag{16}$$

$$\text{Rate of elimination } (\text{RE}) = \text{CL} \times \text{concentration} \tag{17}$$

$$\text{Bioavailability (F\%)} = \frac{\text{AUC } \text{Orral, Sc, Im} \times 100}{\text{AUC}} \tag{18}$$
